Open Access Journal of
Neurology & Neurosurgery
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Opinion
Open Access J Neurol Neurosurg
Copyright © All rights are reserved by Vasiliki E Kalodimou
Volume 1 Issue 3 - October 2016
Mesenchymal Stem Cells Markers
Vasiliki E Kalodimou*
Flow Cytometry-Research & Regenerative Medicine Department, IASO- Maternity & Research Hospital, Greece
Submission: October 05, 2016; Published: October 14, 2016
*Corresponding author: Vasiliki E Kalodimou, Director at Flow Cytometry-Research & Regenerative Medicine Department, IASO- Maternity &
Research Hospital, Athens, Greece, Email:
Opinion
In the field of regenerative medicine, basic research and
preclinical studies have been conducted to overcome clinical
shortcomings with the use of stem cells, mesenchymal stem
cells and adipose stem cells. They are present in adult tissues,
including bone marrow, umbilical cord, umbilical cord blood
and adipose tissue [1]. For many years, bone marrow-derived
stem cells were the primary source of stem cells for tissue
engineering applications. Russian-born Alexander A. Maximow
in 1924 used extensive histological findings to identify a kind of
spherical precursor cell in the mesenchyme, which can grow and
differentiate into Different cell types. In late 1960’s the scientists
Ernest A. McCulloch and James E. Till reveal for the first time the
clonal nature of bone marrow cells [2]. The challenge was to find
those cells that can self-renew and differentiate into three cell
types: bone, cartilage and fat (Figure 1).
Figure 1: Mesenchymal stem cell differentiation: The MSC’s can
differentiate into fat, cartilage and bone cells.
The adipogenic differentiation is usually defined by the
appearance of cells containing intracellular lipid droplets. Both
AT-MSC (ASC) and UC-MSC have been successfully differentiated
into adipocytes. The chondrogenic differentiation capacity
of MSC is evidenced by the formation of shiny cell-spheres
expressing type II collagen in pellet cultures. Enhanced alkaline
phosphatase expression and mineralization assayed by von
Kossa or alizarin red staining indicates the occurrence of
osteogenic differentiation [1,2].
The human mesenchymal stem cells (hMSC’s) are typically
isolated from the mononuclear layer of bone marrow after
separation by centrifugation. The mononuclear cells were
Open Access J Neurol Neurosurg 1(3): OAJNN.MS.ID.55561 (2016)
cultured in medium with 10% fetal calf serum, and adhere to
the walls.
Some of the hematopoietic cells adhere well, but over
time in culture they are lost. Mesenchymal stem cells are
characterized morphologically by a small cell body. The cell body
containing a large, round nucleus surrounded by fine particles
of chromatin in the nucleus, allowing clarity. The remain of the
cell body containing a small amount of Golgi, mitochondria and
polyribosome’s (Figure 2) [2,4]. Mesenchymal stem cells (MSC’s)
are characterized by great “plasticity”, i.e., have the ability to
differentiate to form various cell types. For this reason it can be
used in regenerative medicine to regenerate tissues and organs.
Another important characteristic of the mesenchymal stem cell
proliferation is the ability of these cells, to proliferate without
losing their “plasticity”[2,3].
Figure 2: Mesenchymal stem cell showing typical ultra-structural
morphology.
Beyond that, there is little we can say with confidence.
Numerous studies have shown that human MSC’s avoid selfrecognition and interfere with the dendritic cells and T-cells
and create an immunosuppressive microenvironment of the
cytokines they secrete [5,6]. Other studies contradict some of
these findings, reflecting the highly heterogeneous nature of
MSC isolated and significant differences between the isolated
cells are created by many different methods under development.
The majority of modern techniques still use the approach CFU,
wherein the bone marrow with or without ficoll spreads directly
into cell culture plates or flasks. The mesenchymal stem cells, but
not the red or hematopoietic cells adhere to the plastic medium
within 24 to 48 hours. [7-9].
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Open Access Journal of Neurology & Neurosurgery
The major sources of human mesenchymal stem cells
(MSC) can be distinguished between adult tissues, preferably
bone marrow (BM), peripheral blood (PB) and adipose tissue
(AT) and neonatal birth-associated tissues, including placenta
(PL), umbilical cord (UC) and cord blood (CB) [1,2]. With
flow cytometry sorting we marrow cells to specific surface
markers, such as STRO -1, STRO-1 + cells, which are generally
more uniform, and have higher capacity and higher rates of
proliferation, differentiation, but the exact differences between
STRO-1 + cells and MSC’s they are not clear yet [1,10,11]. The ISCT
(International Society of Cellular therapy), has proposed a set of
standards for determining the MSC. A cell can be characterized
as MSC’s if displays plasticity under normal culture conditions
and has a fibroblast-like morphology.
Moreover, it can be differentiated ex-vivo in bone, fat and
cartilage. Phenotypically express a number of indicators, none of
which is specific to the MSC’s. It is generally accepted that adult
human MSC’s do not express hematopoietic markers (Cells must
show <2% positivity for the expression of cell-surface antigens,
Negative markers): CD45, CD34, CD14, CD11, CD80, CD86, CD40,
CD31, CD18, or CD56, but do express (Cells must show >95%
positivity for the expression of cell-surface antigens, Positive
markers): CD105, CD73, CD44, CD90, CD71, CD106, CD166 and
CD29 (Table 1 & 2). The cultured MSCs also expresses on their
surface markers such as CD73, CD90 and CD105, while lacking
the expression of CD11, CD14, CD19, CD34, CD45, CD79 and
HLA-DR [1,2].
Table 1: Shows the positive and negative expression of MSC markers.
Positive
Markers
Negative
Markers
Cells must express >95% positivity for cell surface
antigen expression: CD29, CD44, CD73, CD90,
CD105, CD166 & CD271.
Cells must express <2% positivity for cell surface
antigen expression: CD14, CD31, CD34, CD45,
CD133 & Lin 1
Table 2: Shows the positive and negative expression according to
major sources of human mesenchymal stem cells.
Positive
Markers
Negative
Markers
Bone Marrow
MSC
Adipose
Tissue MSC
Peripheral Blood
MSC
CD13, CD44,
CD73 (SH3),
CD90, CD105
(SH2), CD166,
STRO-1
CD9, CD13,
CD29, CD44,
CD54, CD73
(SH3), CD90,
CD105 (SH2),
CD106, CD146,
CD166, HLA I,
STRO-1
CD44, CD54, CD90,
CD105 (SH2),
CD166
CD14, CD34,
CD45
CD11b, CD14,
CD19, CD31,
CD45, CD79a,
CD133, CD144,
HLA-DR
CD14, CD34, CD45,
CD31
The MSCs are a promising cell source because
•
•
002
Differentiate into many different cell types in vitro.
Relatively easy to proliferate in culture.
•
Possess immunological traits.
3. Development of mesenchymal stem cells as medical
therapies poses two potential problems
• Cells must be passaged repeatedly to ensure enough
healthy cells available as treatment for a particular disease.
•
MSCs may come from a variety of donors and could
contain populations of cells that vary in their ability to
differentiate, especially after repeated multiplication and
passaging.
Overall Conclusion
•
MSCs can differentiate into a variety of cell types.
•
MSCs expression of cell-surface antigens must show
>95% positivity and <2% negativity.
•
Adult human MSC’s do not express hematopoietic
markers.
•
Cultured MSCs also expresses on their surface markers
•
MSCs are superior to other types of stem cells:
•
They have the potential to treat a wide range of acute
and degenerative diseases.
a.
No ethical issues
b.Immune-privileged
•
Autologous MSC could be used for the regeneration of
human tissues
It is crucial to set standards in order to be safely characterized
and use MSCs as potential therapies in regenerative medicine.
References
1. Kalodimou VE (2013) Basic principles in flow cytometry. AABB Press,
Bethesda, Md, USA.
2. Kalodimou VE (2015) A Handbook to Mesenchymal Stem Cells in
Regenerative Medicine, Speg. Co Press, Greece.
3. Stereodimas A, Kalodimou VE, Nicaretta B (2013) Adipose Derived
Stem Cells characterization from human lipoaspirate: A comparative
study. Journal of Biomimetics, Biomaterials & Tissue Engineering 18:
73-83.
4. Deans RJ, Moseley AB (2000) Mesenchymal stem cells: Biology and
potential clinical uses. Exp Hematol 28(8): 875-884.
5. Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, et al.
(2005) Comparative characteristics of mesenchymal stem cells from
human bone marrow, adipose tissue, and umbilical cord blood. Exp
Hematol 33(11): 1402-1416.
6. Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, et al. (2006) Biologic
properties of mesenchymal stem cells derived from bone marrow and
adipose tissue. J Cell Biochem 99(5): 1285-1297.
7. Trojahn Kolle SF, Oliveri RS, Glovinski PV, Elberg JJ, Fischer-Nielsen A,
et al. (2012) Importance of mesenchymal stem cells in autologous fat
grafting: a systematic review of existing studies. J Plast Surg Hand Surg
46(2): 59-68.
How to cite this article: Vasiliki E K. Mesenchymal Stem Cells Markers. Open Access J Neurol Neurosurg. 2016; 1(3): 555561.
Open Access Journal of Neurology & Neurosurgery
8. Casteilla L, Dani C (2006) Adipose tissue-derived cells: from physiology
to regenerative medicine. Diabetes Metab 32(5 Pt 1): 393-401.
9. Zuk PA, , Zhu M, Mizuno H, Huang J, Futrell JW, et al. (2001) Multiline
age cells from human adipose tissue: implications for cell-based
therapies. Tissue Eng 7(2): 211-228.
10.Folgiero V, Migliano E, Tedesco M, et al. (2010) Purification and
characterization of adipose-derived stem cells from patients with
lipoaspirate transplant. Cell Transplant 19(10): 1225-1235.
11.Kalodimou VE (2014) Adipose mesenchymal stem cells: could be the
future in regenerative medicine? Heart Health Open Access 1: 106.
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How to cite this article: Vasiliki E K. Mesenchymal Stem Cells Markers. Open Access J Neurol Neurosurg. 2016; 1(3): 555561.